Voriconazole Metabolism is Associated with the Number of Skin Cancers Per Patient

TL;DR

This study shows that how patients metabolize voriconazole affects how many skin cancers they develop, especially squamous cell carcinomas, after an organ transplant.

Contribution

The study reveals that voriconazole metabolism, influenced by CYP2C19 phenotype, is linked to increased skin cancer risk in transplant patients.

Findings

Voriconazole-exposed rapid metabolizers had significantly more squamous cell carcinomas after transplant.

Voriconazole exposure was associated with faster development of skin cancers, particularly squamous cell carcinomas.

The association between voriconazole and skin cancer risk was strongest for squamous cell carcinoma.

Abstract

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two (p < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure (p < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19–2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14–2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.

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